Mice, Men, and the Measure of Resveratrol

Mice, Men, and the Measure of Resveratrol

Preventive Medicine Column

Dr. David L. Katz

Based on a small, brief, but nonetheless profound and compelling study in Cell Metabolism, I intend to start taking resveratrol.

The study in question assigned 11 obese but otherwise healthy men to 30 days of placebo and 30 days of 150 mg of resveratrol daily in random order. The study was double-blind, meaning neither the participants nor the researchers knew who was taking what when. The fundamental study hypothesis, based on prior work in animals, was that resveratrol supplementation would mimic the effects of calorie restriction.

Calorie restriction has long shown promise for extending lifespan. Studies in a number of species have shown clear gains in longevity with administration of a nutritionally adequate, but calorically restricted diet (roughly 30% fewer calories than would be considered a ‘normal’ level for maintenance of healthy weight). There have been no such studies in humans, for some fairly obvious reasons- salient among them the fact that if such an intervention worked, it would take longer than the researcher’s lifespan to find out!

That said, the metabolic effects of calorie restriction in humans suggest opportunities for both health promotion, and life extension. But there are also some jokes attached to the notion of extending survival by practicing a state of carefully controlled, semi-starvation. Among the better ones: you may live forever, or maybe it will just feel that way. Or: it may well extend your life, but you’ll keep wishing you would die!

Of course, adherents to so-called ‘CR’ deny the downside, and report feeling vital while anticipating a long life. They intend to have the last laugh. Whether or note they get it, I wish them well.

But I also recognize that no matter what the benefits of calorie restriction, most people will not practice it. After all, we know there are profound benefits of controlling weight just by eating the recommended level of calories- and we can’t get most people to do that! So 30% less? Fuggedaboutit.

Enter resveratrol.

Resveratrol is a compound concentrated in grape skin- and thus red wine. Early studies suggested it functioned as a potent antioxidant, but resveratrol is more than that. It influences mitochondrial function and energy metabolism. And most importantly, resveratrol is a gene modifier. It influences the activity of a gene complex called SIRT1, which in turn influences a wide array of metabolic activity. SIRT1 is considered a regulator of the ‘health span,’ and is the very gene complex affected by calorie restriction.

The new study reports changes in biochemical measures and cell biology and is thus a bit dense in its details. But the take-away message was clear enough. Daily dosing of resveratrol for a month mimicked most effects of calorie restriction, improving energy metabolism in muscle, improving insulin sensitivity, lowering blood pressure, and apparently enhancing fitness. There were no adverse effects of resveratrol seen.

Of course, there is much we don’t know. The beneficial effects of resveratrol might wear off in time, or be too modest to matter. Or perhaps adverse effects might show up late; some have been seen with higher doses over extended periods. Calorie restriction is associated with reduced fertility, and reduced libido. I count myself among those who would consider the latter of those effects too high a price to pay for any metabolic benefits. We don’t know if resveratrol can facilitate weight loss- although that looks promising. We don’t know, and won’t for a very long time, if it can extend the human life span.

But we do have the first clear evidence that a natural compound can exert the same profound effects on metabolism, weight, and genes – in humans- as calorie restriction. There is at least reason to hope a meaningful anti-aging effect could be appreciated as well.

Resveratrol has made the leap from mice to men. It will take some time to ascertain the true medical measure of this compound. While it is certainly premature to declare it a ‘wonder drug,’ I find myself wondering about that possibility. It’s the best contender for a profound medical advance in a pill I have seen in a long time.

And so, I intend to try it for the next 6 months or so to see what effects I discern (less, of course, if I discern any I don’t like!). I can’t yet recommend resveratrol to you with any great conviction, but I can share my excitement about its apparent promise- and I promise to share the results of my personal experience with it. Stay tuned!